DCT
3:22-cv-01810
Fresenius Kabi v. Steriscience Pte Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Fresenius Kabi USA, LLC (Delaware)
- Defendant: Steriscience Pte. Limited (Singapore)
- Plaintiff’s Counsel: Robinson Miller LLC
- Case Identification: 3:22-cv-01810, D.N.J., 03/31/2022
- Venue Allegations: Venue is asserted on the basis that the Defendant is a foreign corporation (incorporated in India) and thus may be sued in any judicial district in the United States.
- Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) for generic levothyroxine sodium for injection constitutes an act of infringement of three patents directed to stable, lyophilized formulations of the drug.
- Technical Context: The technology concerns pharmaceutical formulations of levothyroxine, a synthetic thyroid hormone used for hormone replacement therapy, which are stabilized for storage and intravenous administration.
- Key Procedural History: This is a Hatch-Waxman Act lawsuit initiated after Defendant Steriscience filed ANDA No. 216729 with the FDA, seeking approval to market a generic version of Plaintiff's drug product. The ANDA filing included a "Paragraph IV certification," alleging that Plaintiff's patents-in-suit are invalid, unenforceable, or will not be infringed by the proposed generic product. Plaintiff was formally notified of this certification via a letter dated February 14, 2022.
Case Timeline
| Date | Event |
|---|---|
| 2011-06-24 | Plaintiff's New Drug Application (NDA No. 202231) for Levothyroxine Sodium approved by FDA |
| 2011-08-30 | Earliest priority date for all patents-in-suit |
| 2015-04-14 | U.S. Patent No. 9,006,289 issued |
| 2015-10-27 | U.S. Patent No. 9,168,238 issued |
| 2015-10-27 | U.S. Patent No. 9,168,239 issued |
| 2022-02-14 | Plaintiff received Defendant's Paragraph IV Notice Letter |
| 2022-03-31 | Complaint filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,006,289 - Levothyroxine Formulations
Issued April 14, 2015
The Invention Explained
- Problem Addressed: The patent’s background section states that it is desirable to provide a new formulation of levothyroxine sodium that can "further improve the stability of the levothyroxine," particularly for extended periods above room temperature, compared to conventional formulations (’289 Patent, col. 2:17-21).
- The Patented Solution: The invention is a lyophilized (freeze-dried) solid composition containing levothyroxine sodium, a phosphate buffer, and a specific, relatively low amount of mannitol (’289 Patent, Abstract). The specification explains that improved stability can be achieved by lowering the mass of mannitol and/or the mass ratio of mannitol to levothyroxine compared to conventional formulations, which used significantly more mannitol (’289 Patent, col. 5:19-30).
- Technical Importance: A more stable injectable formulation of levothyroxine is particularly useful for urgent thyroid replacement or when oral administration is not possible, such as for a patient in a state of myxedema coma (’289 Patent, col. 2:1-3).
Key Claims at a Glance
- The complaint asserts independent claim 1 (Compl. ¶41).
- The essential elements of independent claim 1 are:
- A composition, comprising:
- about 100 or about 200 micrograms of levothyroxine sodium;
- a phosphate buffer; and
- from 2 to 4 milligrams of mannitol,
- where the composition is a lyophilized solid.
- The complaint reserves the right to assert claims 1-21 (Compl. ¶40).
U.S. Patent No. 9,168,238 - Levothyroxine Formulations
Issued October 27, 2015
The Invention Explained
- Problem Addressed: The patent addresses the same technical problem as the ’289 Patent: the need for a more stable injectable formulation of levothyroxine sodium (’238 Patent, col. 2:17-21).
- The Patented Solution: The invention is a lyophilized solid composition of levothyroxine sodium with a buffer and a specified low range of mannitol, which provides improved stability (’238 Patent, Abstract). The specification, which is substantially similar to that of the ’289 Patent, teaches that lowering the mannitol-to-levothyroxine ratio improves stability, particularly for the 200 µg and 500 µg dosage strengths (’238 Patent, col. 5:56-65).
- Technical Importance: The invention provides stable formulations covering a range of therapeutically relevant dosages for patients who cannot take oral medication, including those needing an initial high dose (’238 Patent, col. 1:40-48).
Key Claims at a Glance
- The complaint asserts independent claims 1 and 21 (Compl. ¶56).
- The essential elements of independent claim 1 are:
- A lyophilized solid composition, comprising:
- about 100 micrograms of levothyroxine sodium;
- a buffer; and
- between 2 to 4 milligrams of mannitol.
- The essential elements of independent claim 21 are:
- A lyophilized solid composition, comprising:
- about 500 micrograms of levothyroxine sodium;
- a buffer; and
- between 2 to 4 milligrams of mannitol.
- The complaint reserves the right to assert claims 1-30 (Compl. ¶55).
U.S. Patent No. 9,168,239 - Levothyroxine Formulations
Issued October 27, 2015
Technology Synopsis
This patent addresses the chemical instability of conventional levothyroxine formulations for injection (’239 Patent, col. 2:17-21). The patented solution is a lyophilized solid composition comprising a salt of levothyroxine, a buffer, and a specific range of mannitol (2 to 4 milligrams), which is taught to provide greater stability than prior art formulations containing higher amounts of mannitol (’239 Patent, Abstract; col. 5:19-30).
Asserted Claims
The complaint asserts independent claim 1 and dependent claims 2-15 (Compl. ¶70-71).
Accused Features
The complaint alleges that Steriscience's proposed generic products, as described in ANDA No. 216729, are lyophilized solid compositions that will contain a salt of levothyroxine, a buffer, and mannitol within the claimed ranges (Compl. ¶31, ¶33, ¶72).
III. The Accused Instrumentality
Product Identification
The accused products are Steriscience’s generic "levothyroxine sodium for powder for injection" in 100 mcg/vial, 200 mcg/vial, and 500 mcg/vial dosage strengths, for which Steriscience seeks FDA approval via ANDA No. 216729 (Compl. ¶1, ¶31).
Functionality and Market Context
The accused products are proposed generic versions of Fresenius Kabi's approved and commercially marketed levothyroxine drug products (Compl. ¶33). To gain FDA approval, the generic products must be bioequivalent to Fresenius Kabi's products (Compl. ¶29). The complaint alleges the products are intended for the treatment of myxedema coma, an indication for which Fresenius Kabi's products are used (Compl. ¶28).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
'289 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A composition, comprising: about 100 or about 200 micrograms of levothyroxine sodium; | Defendant's ANDA seeks approval for generic products in 100 mcg/vial and 200 mcg/vial strengths. | ¶31, ¶42 | col. 10:1-4 |
| a phosphate buffer; | The complaint alleges on information and belief that the generic product contains each element of the claim, and further alleges the generic is the same or substantially the same as Plaintiff's product, which contains a phosphate buffer. | ¶33, ¶42 | col. 10:5 |
| from 2 to 4 milligrams of mannitol, | The complaint alleges on information and belief that the generic product contains mannitol in the claimed amount. | ¶42 | col. 10:6 |
| where the composition is a lyophilized solid. | Defendant's product is described as a "powder for injection," which the complaint alleges is a lyophilized solid. | ¶1, ¶41 | col. 10:7-8 |
- Identified Points of Contention:
- Scope Questions: The construction of "about" (e.g., "about 100 micrograms") will be relevant, as its interpretation determines the allowable deviation from the recited dosage.
- Technical Questions: A key evidentiary question is whether the accused product actually contains a "phosphate buffer" and mannitol "from 2 to 4 milligrams." The complaint's allegations are made on "information and belief" (Compl. ¶42), and factual confirmation will depend on discovery of the contents of the ANDA.
'238 Patent Infringement Allegations
| Claim Element (from Independent Claims 1 & 21) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A lyophilized solid composition, comprising: about 100 micrograms of levothyroxine sodium; | Defendant's ANDA includes a product with a 100 mcg/vial strength. | ¶31, ¶57 | col. 11:3-4 |
| A lyophilized solid composition, comprising: about 500 micrograms of levothyroxine sodium; | Defendant's ANDA includes a product with a 500 mcg/vial strength. | ¶31, ¶57 | col. 12:22-23 |
| a buffer; | The complaint alleges on information and belief that the generic products for all asserted strengths contain a buffer. | ¶57 | col. 11:5; col. 12:24 |
| between 2 to 4 milligrams of mannitol. | The complaint alleges on information and belief that the generic products contain mannitol in the claimed amount. | ¶57 | col. 11:6; col. 12:25 |
- Identified Points of Contention:
- Scope Questions: The term "a buffer" in the ’238 Patent is facially broader than "a phosphate buffer" in the ’289 Patent. This raises the question of whether an accused product with a non-phosphate buffer could infringe the ’238 Patent but not the ’289 Patent.
- Technical Questions: As with the ’289 patent, the infringement case depends on evidence, presumably from the ANDA, confirming the presence and amounts of the claimed buffer and mannitol. The complaint's allegations rest on "information and belief" (Compl. ¶57).
V. Key Claim Terms for Construction
The Term: "a phosphate buffer" (’289 Patent, Claim 1)
- Context and Importance: The identity of the buffer is a critical limitation separating the claims of the '289 patent from the broader claims of the '238 and '239 patents. Practitioners may focus on this term because if Defendant’s product uses a non-phosphate buffer, it would have a direct non-infringement defense against the ’289 patent.
- Evidence for a Broader Interpretation: The specification discusses "a phosphate buffer" and gives examples such as dibasic or monobasic sodium phosphate, without explicitly limiting the term to those examples (’289 Patent, col. 6:47-51). A party may argue this supports a construction covering any buffer system based on phosphate chemistry.
- Evidence for a Narrower Interpretation: The dependent claims specify particular phosphate buffers and amounts (e.g., "dibasic sodium phosphate in an amount from 400 to 600 micrograms" in claim 4). A party may argue that these specific disclosures should be used to narrow the interpretation of the broader term in the independent claim.
The Term: "about" (e.g., "about 100 micrograms," "about 500 micrograms")
- Context and Importance: This term's construction defines the permissible variance from the specified drug quantity. Practitioners may focus on this term because pharmaceutical manufacturing involves inherent variability, and the precise amount of active ingredient in the accused product could be a point of dispute.
- Evidence for a Broader Interpretation: The patent discloses improved stability across a wide range of dosages (100-500 mcg) and demonstrates that the key inventive concept relates to the ratio of mannitol to levothyroxine, suggesting the invention is not hypersensitive to slight variations in absolute dosage (’289 Patent, col. 8:1-15).
- Evidence for a Narrower Interpretation: The patent’s stability data is presented for discrete dosage amounts (100, 200, and 500 mcg) (’289 Patent, Tables 1-3). A party could argue that in the context of a potent drug, "about" should be construed narrowly to reflect the precision suggested by the examples and required by good manufacturing practices.
VI. Other Allegations
- Indirect Infringement: The primary infringement allegation is the statutory act of filing the ANDA under 35 U.S.C. § 271(e)(2) (Compl. ¶37). The complaint also alleges that upon approval, Defendant will induce infringement by doctors and patients who will use the generic product for its intended and labeled indication of treating myxedema coma (Compl. ¶28).
- Willful Infringement: The complaint alleges that Defendant was aware of the patents-in-suit at the time it submitted its ANDA (Compl. ¶46, ¶61, ¶76). It further alleges that Defendant has "no reasonable basis" for its belief that the patents are invalid or not infringed, forming the basis for a claim of willfulness and a request for a finding that the case is "exceptional" under 35 U.S.C. § 285 (Compl. ¶47-48, ¶62-63, ¶77-78).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central evidentiary question will be one of compositional identity: does the formulation described in Steriscience’s confidential ANDA filing in fact contain the specific excipients—namely, a buffer and mannitol—in the amounts required by the asserted claims? The complaint's allegations are based on "information and belief," making the discovery of the ANDA's contents a dispositive step in the litigation.
- A key legal issue will be one of claim scope differentiation: how will the court construe the distinct terms "a phosphate buffer" (in the ’289 patent) and the broader term "a buffer" (in the ’238 and ’239 patents), given that the patents share a nearly identical specification? This distinction could create different infringement outcomes for the patents if the accused product contains a non-phosphate buffering agent.